Introduction
Ductopenia is defined by loss of ≥50% intrahepatic bile ducts. For an
accurate diagnosis on a liver biopsy, at least 11 portal tracts need to
be evaluated1-2. Ductopenia is associated with a wide
variety of liver pathologies including congenital and genetic diseases
such as biliary atresia and cystic fibrosis, autoimmune diseases such as
primary biliary cholangitis (PBC) and primary sclerosing cholangitis
(PSC), infections such as CMV and HIV, neoplasms such as Hodgkin
lymphoma, ischemic insults, and injuries induced by a large array of
drugs or toxins3. However, some cases have no
identifiable etiology, a phenomenon previously recognized as idiopathic
adulthood ductopenia but now better known as vanishing bile duct
syndrome (VBDS)3-4. These conditions typically present
with chronic cholestasis, although isolated transaminitis has been
reported5-6.
Drug-induced liver injury (DILI) can be divided into hepatitic,
cholestatic or mixed hepatitic and cholestatic patterns clinically.
Microscopically, DILI varies from necroinflammatory injury, cholestatic
injury, steatosis or steatohepatitis, fibrosis with cirrhosis, vascular
lesions, neoplasia, to other rare patterns7.
Drug-induced cholestatic liver injury also takes several forms. The
mildest form is acute cholestasis or bland cholestasis, which shows
intrahepatic cholestasis with minimal inflammation. When intrahepatic
cholestasis is accompanied by necroinflammation and duct injury, it is
cholestatic hepatitis8. Drug-induced cholestatic liver
injury may also be chronic, and can be further divided into PSC-like,
PBC-like, or VBDS pattern8-9. The VBDS pattern was
initially recognized with chlorpromazine, but many other drugs were
later found to be associated with ductopenia9-11.
Ductopenia diagnosed on liver biopsy has been reported as early as three
weeks after the onset of symptoms12. Some sources also
distinguish between acute and chronic drug-induced VBDS, the latter
characterized histologically by the presence of ductular reaction and
copper accumulation7. In certain cases, jaundice and
abnormal liver function tests may eventually resolve, and successful
treatments have been reported13-15. However, VBDS may
also progress to biliary cirrhosis and require liver transplantation
(LT)12,16-18.
Cloxacillin, oxacillin, and flucloxacillin belong to a group of
penicillinase-resistant isoxazolyl penicillins which are often used for
methicillin-sensitive Staphylococcus species,Pneumococcus , and beta-hemolyticStreptococci19 . Flucloxacillin is a well-known
cause of drug-induced cholestasis and particularly
ductopenia12,20-23. In contrast, oxacillin and
cloxacillin have only been reported in cases of acute intrahepatic
cholestasis, with bile accumulation in hepatocytes or canaliculi without
duct loss, or cholestatic hepatitis with associated
inflammation24-26. We present the first case of
cloxacillin-induced acute ductopenia and review the clinicopathologic
features of reported cases of cloxacillin-related liver injury.